The Section on Neurophysiology studies two of the central problems in systems neurobiology: the specialized functions of the frontal cortex and the neural network underlying symbolically guided actions. Much of our research analyzes the role of the frontal cortex in the mapping of symbols to actions. Although symbolic guidance of action is not always recognized as an important issue in mental health research, the capacity to make decisions based on symbols comprises a fundamental feature of daily life activity. Diseases such as schizophrenia, attention deficit-hyperactivity disorder, obsessive-compulsive disorder, and others may result from inappropriate selection and control of actions, typically based on symbolic guidance rather than direct manipulation and control of objects in the environment. In symbolic mapping, the choice of an action to be made depends on the behavioral context provided by a symbol. This is the basis for learning the meaning of most words, for learning to associate that meaning with the motor programs necessary to generate speech and language, and for the wide variety of symbol-guided behavior that underlies a great deal of the most advanced human behavior. The work on this project has shown that symbolically guided action depends upon the proper function of specific parts of the frontal cortex and specific additional parts of the brain such as the hippocampal system and basal ganglia. Our research has been directed at understanding symbolically guided actions in health, so that physicians, therapists, and other health care specialists can one day improve treatments for people who have disabilities in this area. In the past year, the highlights of in this field include: (1) the first empirical support of the theory that cortex and basal ganglia function in distributed modular architectures, commonly known as ?loops? (Brasted and Wise, 2004); (2) the finding that changes occur later in both putamen and premotor cortex than in the hippocampus (Buch, Brasted, and Wise, 2004 abstract); (3) the demonstration that the hippocampal system functions more generally in symbolically guided action than previously believed, and underlies the one-trial learning of nonspatial symbolic associations and with evidence for this learning being subserved by Hebbian mechanisms (Brasted, Bussey, Murray, and Wise, in preparation); and (4) demonstration of neural signals underlying advanced cognitive behavior, specifically the use of rules and strategies in symbolically guided action (Genevesio, Brasted, Mitz, and Wise, 2004 abstract). We also have dispelled the common misconception that the main function of the prefrontal cortex is the maintenance of sensory information in short-term, working memory. We found that attentional signals predominate over memory signals in the dorsolateral prefrontal cortex, contrary to the prevailing theory (Lebedev, Messinger, Kralik, and Wise, 2004). In a major project, the project produced a book on motor learning and memory. The Computational Neurobiology of Reaching and Pointing: A Foundation for Motor Learning, is to be published next January by The MIT Press (Shadmehr and Wise, 2005). Another major writing project built on some experimental work completed a few years ago. This work caught the attention of the organizers of a meeting on psychogenic movement disorders. Psychogenic movement disorders are a common problem presenting to neurologists and psychiatrists, estimated to be 5-20% of patient visits, depending upon the nature of the practice. Patients present with problems of gait difficulties, tremors, jerks, abnormal postures and clumsiness. And these patients are not specific to movement disorders clinics: Such disorders analogues in all of medicine, in which psychogenic disorders also include blindness and anesthesia. Taken together, they compose a major group of "unexplained medical symptoms". According to a noted authority: ?Neurologists often to not know how to deal with such patients, and psychiatrists often do not recognize such patients, thinking that they must have an "organic" disorder.? Currently, the etiology and pathophysiology these disorders remain nearly completely unknown. Indeed, again according to a noted authority on these disorders: ?Most physicians do not even know how to discuss the disorder with the patients. The frequency of such patients and the lack of understanding of the disorder is a crisis for medicine.? In the past year, this project contributed to a theoretical treatment of the psychogenic movement disorders in the context of recent neurophysiological progress in understanding the mechanisms of decision making and choice. According to some recent models of decision, choice, and action, distinct neural networks accumulate evidence in favor of making a potential movement. Voluntary movements arise when one of these networks reaches its threshold for producing an output. Sluggish operations in these networks could prevent an intended movement or make one difficult. Hyperactive networks might generate unintended movements. Other networks operate through similar mechanisms to ?veto? movements, and hyperactive operations in these networks could also prevent intended movements. Taken together with the idea that people might be aware of some of the ?evidence? for making or vetoing a movement, but not all of it, these models provide useful insights into psychogenic movement disorders, and provide a neurobiological basis for discussing these disorders with patients and their families. The contribution from this project will appear in a book that is expected to be published as Wise and Kralik (2005) in Psychogenic Movement Disorders: Psychobiology and Treatment of a Functional Disorder, M. Hallett, S. Fahn, J. Jankovic, A. E. Lang, C. R. Cloniger, and S. C. Yudofsky eds., Lippincott, Williams and Wilkins.